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3230431 
Journal Article 
Prenatal exposure to DEHP affects spermatogenesis and sperm DNA methylation in a strain-dependent manner 
Prados, J; Stenz, L; Somm, E; Stouder, C; Dayer, A; Paoloni-Giacobino, A 
2015 
1 
PLoS ONE
EISSN: 1932-6203 
Public Library of Science 
SAN FRANCISCO 
10 
7 
1-27 
English 
26244509 
WOS:000359061400018 
Di-(2-ethylhexyl)phtalate (DEHP) is a plasticizer with endocrine disrupting properties found ubiquitously in the environment and altering reproduction in rodents. Here we investigated the impact of prenatal exposure to DEHP on spermatogenesis and DNA sperm methylation in two distinct, selected, and sequenced mice strains. FVB/N and C57BL/6J mice were orally exposed to 300 mg/kg/day of DEHP from gestation day 9 to 19. Prenatal DEHP exposure significantly decreased spermatogenesis in C57BL/6J (fold-change = 0.6, p-value = 8.7*10-4), but not in FVB/N (fold-change = 1, p-value = 0.9). The number of differentially methylated regions (DMRs) by DEHP-exposure across the entire genome showed increased hyper- and decreased hypo-methylation in C57BL/6J compared to FVB/N. At the promoter level, three important subsets of genes were massively affected. Promoters of vomeronasal and olfactory receptors coding genes globally followed the same trend, more pronounced in the C57BL/6J strain, of being hyper-methylated in DEHP related conditions. In contrast, a large set of micro-RNAs were hypo-methylated, with a trend more pronounced in the FVB/N strain. We additionally analyze both the presence of functional genetic variations within genes that were associated with the detected DMRs and that could be involved in spermatogenesis, and DMRs related with the DEHP exposure that affected both strains in an opposite manner. The major finding in this study indicates that prenatal exposure to DEHP can decrease spermatogenesis in a strain-dependent manner and affects sperm DNA methylation in promoters of large sets of genes putatively involved in both sperm chemotaxis and post-transcriptional regulatory mechanisms. 
Animals; DNA Methylation/drug effects; Diethylhexyl Phthalate/adverse effects; Endocrine Disruptors/adverse effects; Mice, Inbred C57BL; Mice, Inbred Strains; Plasticizers/adverse effects; Pregnancy; Prenatal Exposure Delayed Effects/chemically induced; Species Specificity; Spermatogenesis/drug effects; Spermatozoa/drug effects; C42K0PH13C 
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